Commentary| Volume 43, ISSUE 4, P762-778, April 2021

Anesthesia and the Developing Brain: A Review of Sevoflurane-induced Neurotoxicity in Pediatric Populations

  • Carol Apai
    Department of Anesthesiology, New Jersey Medical School, Division of Biomedical and Health Sciences, Rutgers University, Newark, NJ, USA
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  • Rohan Shah
    Department of Anesthesiology, New Jersey Medical School, Division of Biomedical and Health Sciences, Rutgers University, Newark, NJ, USA
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  • Khoa Tran
    Department of Anesthesiology, Keck Hospital, Keck Medicine of the University of Southern California, Los Angeles, CA, USA
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  • Shridevi Pandya Shah
    Address correspondence to: Shridevi Pandya Shah, MD, 185 South Orange Avenue, MSB E577, Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ, 07101, USA.
    Department of Anesthesiology, New Jersey Medical School, Division of Biomedical and Health Sciences, Rutgers University, Newark, NJ, USA
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      For over 150 years of anesthetic practice, it was believed that the effects of general anesthetics were temporary and not adverse. A growing number of studies over the past 2 decades, however, have identified structural and cognitive abnormalities, especially in the developing brain. Despite the growing evidence of anesthetic-induced neurotoxicity in animal studies, the evidence to date in humans has been inconsistent and unclear. Sevoflurane, a commonly used inhalational agent in pediatric anesthesia, is an agent of choice for inhalational induction due to its rapid activity and low blood-gas solubility. With evaluation of the current literature, improved considerations can be made regarding the widespread use of sevoflurane as an anesthetic.


      PubMed database was searched for article published between 1969 through 2020. The reference lists of identified articles were searched manually for additional papers eligible for inclusion. This review addressed the tolerability of sevoflurane in specific populations, particularly pediatrics, and is divided into 3 parts: (1) the history of sevoflurane use in anesthetic practice and the pharmacokinetic properties that make it advantageous in pediatric populations; (2) proposed mechanisms of anesthesia-induced neurotoxicity; and (3) considerations due to potential adverse effects of sevoflurane in both short and long procedures.


      There is reason for concern regarding the neurotoxic effects of sevoflurane in both the pediatric and elderly populations, as spatial memory loss, developmental deficits, and an enhanced risk for Alzheimer disease have been linked with the use of this popular inhalational agent.


      The duration and dose of sevoflurane may need to be altered, especially in longer procedures in pediatric populations. This may change how sevoflurane is administered, thus indicating a greater demand for an understanding of its limitations as an anesthetic agent.

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